The proposed research is a continuation of investigations with minimal deviation hepatomas which have demonstrated the existence of a number of differences in the structure and metabolism of lipids relative to normal liver. The detailed characterization of the individual lipid classes at the molecular species level will be extended to plasma membranes and organelle fractions to determine which subcellular structures are affected. The origin of hepatoma lipids will be examined in a number of ways. Lipid requirements and the effects of various lipids on the growth and morphology of cultured hepatoma cells will be examined. The relationship between the lipids of the host's circulation system and a solid host grown hepatoma will be studied in the intact animal and the perfused hindquarters bearing hepatomas. These data will indicate to what extent the hepatoma depends on lipids derived from the host organism. Lipid metabolism studies will be carried out with cultured hepatoma cells, hepatocytes isolated from normal liver, and the host grown hepatoma using various labeled substrates to determine what lipids the hepatoma can synthesize. A comparison of the data will also indicate errors in biosynthesis or catabolism, loss of enzyme specificities, differences in turnover rates, and differences in metabolic routes between the normal and neoplastic hepatocytes. Data from all the proposed experiments will indicate: 1) the dependence and independence of the hepatoma on the lipids from the host's circulation system; 2) differences in lipid structure and metabolism between hepatomas and normal liver; and 3) the effect of dietary lipids on the growth and lipid metabolism of the hepatoma. These data will permit the evaluation of the therapeutic potential of controlling lipid metabolism in neoplasms as a means of controlling their growth.